NF-κB activation is an early event of changes in gene regulation for acquiring drug resistance in human adenocarcinoma PC-9 cells.
NF-κB activation is an early event of changes in gene regulation for acquiring drug resistance in human adenocarcinoma PC-9 cells.
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DOI：
10.1371/journal.pone.0201796
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hohjoh H
中科院分区：
文献类型：
--
作者：
Fukuoka M;Yoshioka K;Hohjoh H
吉非替尼和厄洛替尼是表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）。虽然EGFR-TKI作为抗癌药物是有效的，但癌细胞有时会对药物产生耐受性。以前的研究表明，成纤维细胞生长因子受体（FGFR）信号通路可以作为EGFR信号通路的补偿抑制EGFR-TKI。我们的研究进一步表明，从被吉非替尼杀死的幼稚细胞中泄漏的FGFR配体FGF 2可以启动存活细胞中的FGFR信号通路;即，在EGFR-TKI处理后立即在幼稚细胞中可能发生利他存活。利他主义的生存可能是暂时的，细胞需要改变它们的基因调控以获得对EGFR-TKI的抗性。EGFR-TKI治疗后这种基因调控的变化知之甚少。在这项研究中，我们研究了人类腺癌PC-9细胞中这种基因调控变化的早期事件，这些变化能够改变其对EFGR-TKI的敏感性。我们的研究表明，在EGFR-TKI处理后立即在细胞中发生核因子-κ B（NF-κB）活化，并且还通过针对致癌EGFR的基因沉默发生活化;并且，用于抑制NF-κB活化的MG 132处理影响细胞活力。综上所述，我们的研究结果（包括先前的研究）表明，利他生存和NF-κB激活可能是启动获得EGFR-TKI耐药至关重要。
Gefitinib and erlotinib are epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Although EGFR-TKIs are effective as anti-cancer drugs, cancer cells sometimes gain tolerance to the drugs. Previous studies suggested that the fibroblast growth factor receptor (FGFR)-signaling pathway could serve as compensation for the EGFR-signaling pathway inhibited by EGFR-TKIs. Our study further suggested that FGF2, a FGFR ligand, leaked out from naïve cells killed by gefitinib could initiate the FGFR-signaling pathway in surviving cells; i.e., altruistic survival may occur in naïve cells immediately after EGFR-TKI treatment. Altruistic survival may be temporal, and cells need to change their gene regulation toward gaining resistance to EGFR-TKIs. Changes in such gene regulation after EGFR-TKI treatment are poorly understood. In this study, we examined early events of such gene regulation changes in human adenocarcinoma PC-9 cells that are capable of changing their nature from susceptibility to resistance to EFGR-TKIs. Our study indicated that activation of nuclear factor-kappa B (NF-κB) occurred in the cells immediately after EGFR-TKI treatment and also by gene silencing against oncogenic EGFR; and, MG132 treatment for inhibiting NF-κB activation affected cell viability. Taken together, our findings (including the previous study) suggest that altruistic survival and NF-κB activation might be vital for initiating the acquisition of EGFR-TKI resistance.
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影响因子：
11.2
作者：
Ogino, Atsuko;Kitao, Hiroyuki;Tanimoto, Mitsune
通讯作者：
Tanimoto, Mitsune
影响因子：
3.7
作者：
Takahashi M;Chiyo T;Okada T;Hohjoh H
通讯作者：
Hohjoh H
影响因子：
8
作者：
Gazdar, A. F.
通讯作者：
Gazdar, A. F.
DOI：
10.1016/j.bbrc.2016.09.092
发表时间：
2016-10-14
影响因子：
3.1
作者：
Takahashi, Masaki;Fukuoka, Masashi;Hohjoh, Hirohiko
通讯作者：
Hohjoh, Hirohiko
影响因子：
6.2
作者：
Ware, K. E.;Hinz, T. K.;Kleczko, E.;Singleton, K. R.;Marek, L. A.;Helfrich, B. A.;Cummings, C. T.;Graham, D. K.;Astling, D.;Tan, A-C;Heasley, L. E.
通讯作者：
Heasley, L. E.